TY - JOUR
T1 - Recurrent Respiratory Syncytial Virus Infection in a CD14-Deficient Patient
AU - Besteman, Sjanna B.
AU - Phung, Emily
AU - Raeven, Henriette H.M.
AU - Amatngalim, Gimano D.
AU - Rumpret, Matevž
AU - Crabtree, Juliet
AU - Schepp, Rutger M.
AU - Rodenburg, Lisa W.
AU - Siemonsma, Susanna G.
AU - Verleur, Nile
AU - van Slooten, Rianne
AU - Duran, Karen
AU - van Haaften, Gijs W.
AU - Beekman, Jeffrey M.
AU - Chang, Lauren A.
AU - Meyaard, Linde
AU - van der Bruggen, Tjomme
AU - Berbers, Guy A.M.
AU - Derksen, Nicole
AU - Nierkens, Stefan
AU - Morabito, Kaitlyn M.
AU - Ruckwardt, Tracy J.
AU - Kurt-Jones, Evelyn A.
AU - Golenbock, Douglas
AU - Graham, Barney S.
AU - Bont, Louis J.
N1 - © The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].
PY - 2022/8/24
Y1 - 2022/8/24
N2 - BACKGROUND: Recurrent respiratory syncytial virus (RSV) infection requiring hospitalization is rare and the underlying mechanism is unknown. We aimed to determine the role of CD14-mediated immunity in the pathogenesis of recurrent RSV infection. METHODS: We performed genotyping and longitudinal immunophenotyping of the first patient with a genetic CD14 deficiency who developed recurrent RSV infection. We analyzed gene expression profiles and interleukin (IL)-6 production by patient peripheral blood mononuclear cells in response to RSV pre- and post-fusion (F) protein. We generated CD14-deficient human nasal epithelial cells cultured at air-liquid interface (HNEC-ALI) of patient-derived cells and after CRISPR-based gene editing of control cells. We analyzed viral replication upon RSV infection. RESULTS: Sanger sequencing revealed a homozygous single-nucleotide deletion in CD14, resulting in absence of the CD14 protein in the index patient. In vitro, viral replication was similar in wild-type and CD14-/- HNEC-ALI. Loss of immune cell CD14 led to impaired cytokine and chemokine responses to RSV pre- and post-F protein, characterized by absence of IL-6 production. CONCLUSIONS: We report an association of recurrent RSV bronchiolitis with a loss of CD14 function in immune cells. Lack of CD14 function led to defective immune responses to RSV pre- and post-F protein without a change in viral replication.
AB - BACKGROUND: Recurrent respiratory syncytial virus (RSV) infection requiring hospitalization is rare and the underlying mechanism is unknown. We aimed to determine the role of CD14-mediated immunity in the pathogenesis of recurrent RSV infection. METHODS: We performed genotyping and longitudinal immunophenotyping of the first patient with a genetic CD14 deficiency who developed recurrent RSV infection. We analyzed gene expression profiles and interleukin (IL)-6 production by patient peripheral blood mononuclear cells in response to RSV pre- and post-fusion (F) protein. We generated CD14-deficient human nasal epithelial cells cultured at air-liquid interface (HNEC-ALI) of patient-derived cells and after CRISPR-based gene editing of control cells. We analyzed viral replication upon RSV infection. RESULTS: Sanger sequencing revealed a homozygous single-nucleotide deletion in CD14, resulting in absence of the CD14 protein in the index patient. In vitro, viral replication was similar in wild-type and CD14-/- HNEC-ALI. Loss of immune cell CD14 led to impaired cytokine and chemokine responses to RSV pre- and post-F protein, characterized by absence of IL-6 production. CONCLUSIONS: We report an association of recurrent RSV bronchiolitis with a loss of CD14 function in immune cells. Lack of CD14 function led to defective immune responses to RSV pre- and post-F protein without a change in viral replication.
KW - CD14
KW - epithelium
KW - monocyte
KW - respiratory syncytial virus
KW - Toll-like receptor
KW - Lipopolysaccharide Receptors/deficiency
KW - Cytokines
KW - Humans
KW - Respiratory Syncytial Virus, Human
KW - Leukocytes, Mononuclear/metabolism
KW - Respiratory Syncytial Virus Infections
UR - http://www.scopus.com/inward/record.url?scp=85137126078&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiac114
DO - 10.1093/infdis/jiac114
M3 - Article
C2 - 35429403
AN - SCOPUS:85137126078
SN - 1537-6613
VL - 226
SP - 258
EP - 269
JO - The Journal of infectious diseases
JF - The Journal of infectious diseases
IS - 2
ER -